The relationship between blood levels and clinical efficacy of neuroleptics remains undetermined. Haloperidol (HAL) lacks multiple active metabolites and is therefore a suitable drug for studies of such a relationship. Several small studies claimed that optimal therapeutic results in schizophrenia can be obtained when HAL blood levels were in a "therapeutic range". Levels below and above the range were associated with poorer outcomes. Other workers were unable to confirm the existence of a therapeutic range. The principal goal of this project is to define how HAL and reduced haloperidol (RHAL) blood levels interact with clinical variables in determining the short-term outcome of treatment in schizophrenia and schizoaffective disorder. The subjects will be 135 acutely decompensated new admissions to inpatient services. Patients will be assigned to one of three plasma level ranges of HAL (rather than to a fixed dose), and those who fail to improve after 6 weeks on that plasma level will be either continued in the same range or moved to one of the two other plasma level ranges for another six weeks. Assignment of plasma level ranges will be randomized, and double-blind procedures will be used. The patient evaluations will include the Brief Psychiatric Rating Scale, scales for the assessment of positive and negative symptoms (Andreasen), Simpson-Angus Scale, and special ratings for akathisia. Blood for HAL and RHAL assays will be drawn weekly; HAL plasma levels will be reported on the same day and used for dose adjustment which may be needed to keep the patients within their assigned plasma level ranges. We hypothesize that patients' history and clinical presentation will co-determine the relationship between HAL (and RHAL) blood levels and the outcome. The relationship will be either curvilinear (implying a therapeutic range) or linear. The proposed study will resolve the controversy surrounding the relation between blood levels of HAL and clinical effects. The results will indicate which patients do best at which blood levels of HAL; this will be a major contribution to the clinical practice of psychiatry.